A major non-specific, immediate defense against microbial invasion is a reduction in concentration of free iron, mediated in part by transferrin and lactoferrin. Non-specific defenses such as iron-withholding are most likely to be critical during the fetal and neonatal periods when immune responsiveness is poor. Selection at the transferrin locus has been demonstrated in a variety of species; we have preliminary evidence in horses that reproductive performance is correlated with the geontype of the dam. We propose to determine genotype frequencies for transferrin and other proteins which may be subject to selective pressures from microorganisms (immunoglobulins and complement components) in infants with bacterial infection and in appropriate controls. Additionally, maternal genotypes will be correlated with the history of abortion, stillbirth and prematurity. These studies in humans will be supplemented by an examination of the relationships between transferrin genotypes and fertility in horses, for whom extensive and detailed breeding records are available. Selection against the infant based on maternal genotype has received scant attention in man, although this mechanism of selection has been demonstrated in other species. A correlation between susceptibility to infection and genetic variants of transferrin and/or other proteins would represent a substantial advance in the genetics of disease susceptibility and might have implications for therapeutics.